Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
---|---|---|---|---|
11884470 | Activation of nuclear orphan receptor NURR1 transcription by NF-kappa B and cyclic adenosi | 2002 Mar 15 | Modulation of the NURR subfamily of nuclear receptors may be an important mechanism regulating pathways associated with inflammatory joint disease. We examined the signaling mechanisms through which inflammatory mediators, produced by rheumatoid arthritis (RA) synovial tissue, contribute to the regulation of the NURR subfamily. Markedly enhanced expression of NURR1 is observed in synovial tissue of patients with RA compared with normal subjects. Modulation by proinflammatory mediators in primary RA and normal synoviocytes shows that PGE(2), IL-1beta, and TNF-alpha markedly enhance NURR1 mRNA and protein levels in contrast to other subfamily members, NUR77 and NOR-1. We have established that transcriptional activation of the NURR1 gene by IL-1beta and TNF-alpha requires a proximal promoter region that contains a consensus NF-kappaB DNA-binding motif. IL-1beta- and TNF-alpha-induced NF-kappaB binding to this site is due predominantly to p65-p50 heterodimer and p50 homodimer subunit protein complexes. We further demonstrate a direct CREB-1-dependent regulation by PGE(2) situated at promoter region -171/-163. Moreover, analyses confirm the presence of CREB-1 and NF-kappaB p50 and p65 subunit binding to the NURR1 promoter under basal conditions in freshly explanted RA synovial tissue. In summary, enhanced NF-kappaB- and CREB-1-binding activity on the NURR1 promoter by inflammatory mediators delineates novel mechanisms in the regulation of NURR1 transcription. PGE(2)-, TNF-alpha-, and IL-1beta-dependent stimulation of the NURR1 gene implies that NURR1 induction represents a point of convergence of at least two distinct signaling pathways, suggesting an important common role for this transcription factor in mediating multiple inflammatory signals. | |
12847699 | Osteoprotegerin protects against generalized bone loss in tumor necrosis factor-transgenic | 2003 Jul | OBJECTIVE: To investigate the role of tumor necrosis factor (TNF) in systemic bone loss of chronic inflammatory conditions, such as rheumatoid arthritis (RA), and to address the therapeutic potential of osteoclast blockade. METHODS: We investigated systemic bone changes in human TNF transgenic (hTNFtg) mice, which spontaneously developed severe inflammatory arthritis. RESULTS: Osteodensitometry revealed a significant decrease in trabecular bone mineral density (BMD) (-37%) in hTNFtg mice, and histomorphometry revealed a dramatic loss of bone volume (-85%) compared with wild-type controls. Osteoclast-covered bone surface and serum levels of deoxypyridinoline crosslinks were significantly elevated, suggesting increased osteoclast-mediated bone resorption in hTNFtg mice. Osteoprotegerin (OPG) completely blocked TNF-mediated bone loss by increasing BMD (+89%) and bone volume (+647%). Most strikingly, formation of primary spongiosa was dramatically increased (+563%) in hTNFtg mice after OPG treatment. Osteoclast-covered bone surface and serum levels of deoxypyridinoline crosslinks were significantly decreased by OPG, suggesting effective blockade of osteoclast-mediated bone resorption. OPG did not influence levels of hTNF, TNF receptor I (TNFRI), interleukin-1beta (IL-1beta), and IL-6. However, OPG decreased bone formation parameters (osteoblast-covered bone surface and serum osteocalcin levels), which were elevated in hTNFtg mice. In contrast to OPG, bisphosphonates and anti-TNF treatment did not affect generalized bone loss in hTNFtg mice. Anti-TNF, however, did not affect levels of TNF and TNFRI at the concentrations tested. These data indicate that generalized bone loss due to increased TNF can be blocked by OPG. CONCLUSION: OPG may represent a potent tool for preventing generalized loss of bone mass in chronic inflammatory disorders, especially RA. | |
15283449 | Phantoms in rheumatology. | 2004 | This paper examines rheumatology pain and how it may relate to amputee phantom limb pain (PLP), specifically as experienced in rheumatoid arthritis, fibromyalgia and complex regional pain syndrome (CRPS). Clinical findings, which suggest cortical sensory reorganization, are discussed and illustrated for each condition. It is proposed that this sensory reorganization generates pain and altered body image in rheumatology patients in the same manner as has previously been hypothesized for amputees with PLP; that is via a motor/sensory conflict. The correction of this conflict through the provision of appropriate visual sensory input, using a mirror, is tested in a population of patients with CRPS. Its analgesic efficacy is assessed in those with acute, intermediate and chronic disease. Finally, the hypothesis is taken to its natural conclusion whereby motor/sensory conflict is artificially generated in healthy volunteers and chronic pain patients to establish whether sensory disturbances can be created where no pain symptoms exists and exacerbated when it is already present. The findings of our studies support the hypothesis that a mismatch between motor output and sensory input creates sensory disturbances, including pain, in rheumatology patients and healthy volunteers. We propose the term 'ominory' to describe the central monitoring mechanism and the resultant sensory disturbances as a dissensory state. | |
11830427 | The ICIDH-2 as a framework for the assessment of functioning and disability in rheumatoid | 2002 Mar | OBJECTIVE: To investigate by a cross sectional study in patients with rheumatoid arthritis (RA) the relationship between measures of impairment, activity limitation, and participation of the model of functioning and disability (ICIDH-2). METHODS: Inclusion data of patients with RA (n=803) from the Swiss Clinical Quality Management Group were used. Impairments were measured by the Short Form-36 (SF-36) bodily pain scale, rheumatoid arthritis disease activity index (RADAI), disease activity score (DAS28), and radiographic scoring (x ray). Activity limitation was measured with the Health Assessment Questionnaire (HAQ) and the SF-36 physical functioning scale. Participation was measured with the SF-36 role and social functioning scales. Spearman (partial) correlations were used for analysis. RESULTS: Impairment and activity limitation dimensions of the ICIDH-2 model are related; correlations with the HAQ were: SF-36 bodily pain (r(s)=-0.61), RADAI (r(s)=0.58), DAS28 (r(s)=0.49), and x ray (r(s)=0.35). Similar correlations were found for SF-36 physical functioning. Activity limitation and participation restriction dimensions are also related: the HAQ correlates well with SF-36 role-physical (r(s)=-0.53) and SF-36 social functioning (r(s)=-0.43); SF-36 physical functioning correlates similarly. For impairment and participation restriction dimensions only SF-36 bodily pain is substantially correlated (r(s)=0.47 and 0.48) with SF-36 role-physical, after correcting for the influence of the activity limitation dimension (HAQ and SF-36 physical functioning). CONCLUSIONS: In this cross sectional study of patients with RA, impairments are associated with activity limitations, and activity limitations are associated with participation restrictions. Pain is the only impairment directly associated with participation restrictions. Based on the results of this study, it is strongly recommended that the ICIDH-2 framework is used in clinical trials and observational studies including the assessment of disease consequences in RA. | |
15063084 | Historical review: Cytokines as therapeutics and targets of therapeutics. | 2004 Apr | Cytokine research has spawned the introduction of new therapies that have revolutionized the treatment of many important diseases. These therapeutic advances have resulted from two very different strategies. The first therapeutic strategy embodies the administration of purified, recombinant cytokines. The second relies on the administration of therapeutics that inhibit the harmful effects of upregulated, endogenous cytokines. Examples of successful cytokine therapeutics include hematopoietic growth factors (colony stimulating factors) and interferons. Prime examples of cytokine antagonists that have profoundly altered the treatment of some inflammatory disorders are agents that inhibit the effects of tumor necrosis factor (TNF). In this article, we highlight some of the studies that have been responsible for the introduction of cytokine and anti-cytokine therapies, with emphasis on the development of interferons and anti-TNF agents. | |
15180092 | The natural history and prognosis of rheumatoid arthritis: association of radiographic out | 2004 | OBJECTIVE: The purposes of the present study were: 1) to investigate how the long-term course of outcome and inflammatory variables could be described in individual patients and suitably summarized in groups of patients; 2) to investigate the associations between outcome and inflammatory variables on the basis of the defined summary measures; and 3) to investigate new prognostic aspects of RA by means of frozen sera and DNA specimens. PATIENTS AND METHODS: During the period 1966-78, 685 Danish Caucasian patients with RA, classified according to the 1958 American Rheumatism Association (ARA) criteria, were admitted to the Department of Rheumatology of Aarhus University Hospital. For scientific purposes all patients went through the same examination programme, including biochemical variables, clinical evaluation of 68 diarthrodial joints, and radiographic evaluation of 46 diarthrodial joints. Since 1987, data from these patients have been organized in a database. The data are arranged according to onset of disease. This thesis is based on about 600,000 data-points from 257 patients. RESULTS: The thesis is based on six studies. The first study shows that early symptomatic improvement of RA during gold treatment was stable over several years, but when evaluated radiographically, the condition continued to deteriorate. In the second study, six main types of radiographic progression were identified: (a) a rare type with no radiographic progression at all (<1%); (b) a type with a slow or moderate onset, but an increasing progression rate (exponential growth type) (9%); (c) a linear type (30%); (d) a type with a moderate to fast onset, and a stable progression rate (the square root type) (11%); (e) a type with a fast onset, but a later decreasing progression rate (the first order kinetics type) (30%) and (f) a type characterized by slow onset, then acceleration and later deceleration (the sigmoid type) (20%). The fact that there was a systematic progression was used to define a system of radiographic events, which could be used as outcome measures in prediction models of the long-term course of RA. The third study shows that low serum levels of the complement-activating serum lectin, mannan (mannose) binding protein (lectin) (MBP = MBL), are associated with a higher erythrocyte sedimentation rate (ESR) (p=0.006), joint swelling score (JS score) (p=0.019), limitation of joint motion score (LM score) (p=0.027), and annual increase in radiographic destruction score (R score) (p=0.053). The fourth study demonstrated a highly significant association between summary measures of inflammatory variables and radiographic outcome, as defined in the second study, indicating that the degree of inflammation is important for the development of destructive joint damage in RA. The fifth study showed that MBL-insufficient patients (two defective structural MBL alleles, or one defective allele combined with a low-expression variant of the normal allele) had a relative risk of a severe radiographic event of 3.1 compared with the MBL competent group (p<0.0001). The sixth study showed that the relative risk (RR) of early interleukin (IL)-1alpha auto-antibodies (aAb) positive patients developing serious radiographic joint destruction was significantly lower than for IL-1alpha aAb-negative patients, RR=0.29 (p=0.04). In rheumatoid factor (RF) positive patients RR was only 0.18 (p=0.02). Patients who seroconverted >2 years after the onset of RA showed the most aggressive development of joint erosion, with RR of serious radiographic joint destruction of 2.56 (p=0.048). Other factors investigated in subgroups of the patients were HLA-DR4, chemokine receptor 5 (CCR 5) genotypes. IL-6 aAb, vascular endothelial growth factor (VEGF) aAb, and interferon (IFN)-gamma aAb. About 80% of the patients were HLA-DR4 positive, indicating the importance of HLA-DR4 as a predisposing factor for RA. There was no association between IL-6 aAb and radiographic outcome, or CCR5 genotypes and radiographic outcome. VEGF aAb and IFN-gamma aAb were quantitatively unimportant. CONCLUSION: In spite of a general improvement in single measures of inflammatory variables, and a general deterioration in radiographic outcome of RA, there is a highly significant association between summary measures of inflammatory variables and radiographic outcome. The progression of radiographic damage in RA follows mathematical patterns. A new method of evaluating the long-term radiographic outcome by means of Kaplan-Meier plots is demonstrated. It is shown that MBL and IL-1alpha aAb are predictors of the prognosis of RA and may play important roles in the pathogenesis of RA. | |
12794379 | [Differential diagnosis of acute arthritis]. | 2003 | Acute arthritis can first present as a symptom of dangerous and rapidly progressing disease. It is quite easy to differentiate between arthritis and periarthritis. More problematical is correct early differential diagnosis of the acute arthritis. Determining whether one, several or many joints are affected can narrow the diagnostic possibilities. Arthrocentesis and synovial fluid testing provide much information and should be done at initial evaluation if possible. The presence or absence of fever, rash, family history of joint disease and exposure to infective organisms can further direct diagnostic studies and treatment. In general, to avoid masking clues, drug therapy should be delayed for mild symptoms until diagnosis is complete. This article is designed mostly for primary care physicians, residents and includes author's original data and review of recommended reading. | |
15188330 | High work disability rate among rheumatoid arthritis patients in Lithuania. | 2004 Jun 15 | OBJECTIVE: To evaluate labor force characteristics among patients with rheumatoid arthritis (RA) in Lithuania. To assess if Lithuania's transition from a state-planned to a free-market economy after 1990 changed the employment perspectives of patients with RA. METHODS: RA patients, age 16-65 years (n = 238), were randomly selected from the RA register in Vilnius. They completed questions about sociodemographics, working status, and disease characteristics, they underwent a clinical examination, and they completed the modified Health Assessment Questionnaire and the Short Form 36. RESULTS: Age- and sex-adjusted employment was 24.2% lower and work disability 51.7% higher in patients compared with the general population in Lithuania. After 10 years of disease, 48% of the patients had withdrawn from the labor force. In those with a paid job, the average sick leave in the past year was 31.9 days compared with the national average of 10.8 days. Although disease activity was not significantly different in employed compared with work-disabled patients, physical function and perceived quality of life (except general health) were worse among patients with work disability. The change in economic organization in 1990 was noted to increase the risk for work withdrawal by a factor of 2.75 (95% confidence interval 1.68-4.53). CONCLUSION: In Lithuania, the impact of RA on work disability is important. Although work disability in Lithuanian patients with RA seems more pronounced compared with reports from Western societies, variables associated with work disability are comparable. The transition to a market-orientated economy in 1990 increased the risk of becoming work disabled. | |
12010575 | Production of interleukin-1 receptor antagonist by human articular chondrocytes. | 2002 | Interleukin-1 receptor antagonist (IL-1Ra) is a natural IL-1 inhibitor possessing anti-inflammatory properties. IL-1Ra is produced as different isoforms, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, icIL-1Ra2 and icIL-1Ra3), derived from the same gene. We examined the production of IL-1Ra species by cultured human articular chondrocytes in response to various cytokines. The levels of IL-1Ra were undetectable in culture supernatants of untreated cells, but were significantly increased by IL-1beta. Cell lysates contained very low levels of IL-1Ra, even in response to IL-1beta, suggesting that chondrocytes produce predominantly sIL-1Ra. IL-6, which had no effect on its own, enhanced the effect of IL-1beta, while dexamethasone prevented the response. We observed by RT-PCR that IL-1beta and IL-6 induced primarily the production of sIL-1Ra mRNA. Furthermore, IL-1beta alone or combined with IL-6 increased the levels of nascent unspliced sIL-1Ra mRNA, suggesting that sIL-1Ra expression is regulated at the transcriptional level. Reporter gene assays in immortalized chondrocytes, C-20/A4, consistently showed increased sIL-1Ra promoter activity in response to IL-1beta and IL-6. In conclusion, human articular chondrocytes produce sIL-1Ra in response to IL-1beta and IL-6. The production of sIL-1Ra by chondrocytes may have a protective effect against articular inflammatory and catabolic responses. | |
12508767 | A one year followup of chronic arthritis following rubella and hepatitis B vaccination bas | 2002 Nov | OBJECTIVES: This analysis examined the incidence rate of chronic arthritis adverse reactions reported following adult rubella and hepatitis B vaccinations. In this analysis, etiologic mechanisms for chronic arthritis following adult rubella and hepatitis B vaccines were also explored. METHODS: The Vaccine Adverse Events Reporting System (VAERS) database was analyzed for the incidence rate of reported cases of chronic arthritis in comparison to Tetanus-diphtheria (Td) and tetanus toxoid adult vaccine control groups. RESULTS: Chronic arthritis adverse reactions following adult rubella vaccination were primarily reported in females (female/male ratio = 3.0), at about 45 years-old, and at a mean onset time of 10-11 days following vaccination. Chronic arthritis adverse reactions following adult hepatitis B vaccination were also primarily reported in females(female/male ratio = 3.5), at about 33 years-old, and with a mean onset time of 16 days following vaccination. The incidence rates of chronic arthritis following adult rubella and adult hepatitis B vaccinations were statistically significantly increased, by chi 2 analysis, in comparison to the adult vaccine control groups. The attributable risk of chronic arthritis following adult rubella vaccine ranged from 32 to 53 and from 5.1 to 9.0 following adult hepatitis B vaccine in comparison to the adult vaccine control groups. CONCLUSION: This study revealed that adult rubella and adult hepatitis B vaccines were statistically associated with chronic arthritis which persisted for at least one year. The etiology for these adverse reactions may involve autoimmune mechanisms. Furthermore, potential biases in the reporting rates of adverse reactions to VAERS were not observed. | |
11908557 | The acute phase response does not fully predict the presence of insulin resistance and dys | 2002 Mar | OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased mortality rate from cardiovascular disease. This may relate to insulin resistance and dyslipidemia, which were both reported to correlate with the acute phase response in RA. We investigated whether insulin resistance and dyslipidemia could be explained by the acute phase response as well as excess weight in inflammatory arthritis. METHODS: We investigated 87 patients, 38 with RA, 29 with spondyloarthropathy, 20 with undifferentiated inflammatory arthritis. Thirty age, sex, and race matched healthy volunteers served as controls. Fasting blood samples were taken for determination of erythrocyte sedimentation rate (ESR), plasma glucose, serum insulin, and total cholesterol (chol), low density lipoprotein cholesterol (LDL-chol), high density lipoprotein cholesterol (HDL-chol), and triglycerides. Insulin resistance was estimated by the homeostasis model assessment for insulin resistance (HOMA) and the quantitative insulin sensitivity check index (QUICKI). RESULTS: In controls the mean (SD) HOMA (microU x mmol/ml x l), QUICKI, body mass index (BMI, kg/m2), and ESR (mm/h) were 1.1 (0.5), 0.393 (0.048), 22.9 (2.8), and 13 (8) in patients; they were 1.9 (1.3), 0.357 (0.037), 26.5 (4.2), and 26 (18) in controls, respectively. Each of these differences was highly significant (p < 0.001). HDL-chol concentrations were lower (p = 0.002) and chol/HDL-chol ratios and triglyceride levels were higher (p < 0.001 and p = 0.004, respectively) in patients compared to controls. A high ESR predicted insulin resistance and dyslipidemia, while a high BMI similarly predicted insulin resistance but not dyslipidemia. After controlling for ESR and BMI, insulin sensitivity was no longer different between patients and controls, while HDL-chol concentrations remained lower (p = 0.015) and chol/HDL-chol ratios remained higher (p = 0.003) in patients compared to controls. CONCLUSION: Insulin resistance and dyslipidemia were highly prevalent in patients with inflammatory arthritis. The acute phase response and excess weight could fully explain the insulin resistance but only partially explain the dyslipidemia. These findings have important implications for the management of inflammatory arthritis. | |
15115313 | The L1 retroelement-related p40 protein induces p38delta MAP kinase. | 2004 Feb | We characterized a full length L1 mRNA in a rheumatoid arthritis (RA) synovial tissue and determined the degree of methylation of its 5'-UTR. We asked whether not only intact but also altered L1s can exert biological activities by transfecting RA synovial fibroblasts (SF) with either retrotransposition-competent or incompetent L1s and examined their capacity to induce p38delta. Total RNA was isolated from the synovial tissue of a 35-year-old woman with highly destructive RA. A complete L1 sequence was obtained by 3'/5'-RACE. Methylation of the genomic 5'-UTR was determined by the sodium-disulfide/PCR method. RA-SF were transfected by lipofection with either a functional L1 or an ORF2-mutated L1 element. The expression of p38delta was measured by RT-PCR and Western blot. The full length L1 mRNA included a 5'-UTR, an ORF1 and an ORF2. Three of five CpG islands (60%) of the genomic L1 5'-UTR were hypomethylated and the ORF2 was deactivated by the insertion of stop codons. Both, intact and ORF2-mutated L1 vectors, induced the expression of p38delta. Thus, even an ORF2-mutated L1 element, as expressed in RA, is biologically active and both L1 ORF1 and p38delta transcripts may appear as a consequence of genomic hypomethylation. The induction of p38delta appears to be mediated by an ORF1/p40-dependent process. This is the first indication of a p40 mediated transactivation. | |
14624179 | Comprehensive nursing approach to infliximab infusion therapy. | 2003 Nov | Rheumatoid arthritis (RA) is an immunologically mediated disorder characterized by progressive joint destruction that leads to significant impairment of functioning and quality of life. Its signs and symptoms vary, depending on disease activity. The goals of therapy in patients with RA include a reduction of symptoms, inhibition of structural damage, and improvement in physical function. The paradigm for managing RA calls for adopting a three-pronged strategy that addresses the different aspects of the disease. Infliximab, a biologic response modifier, has been shown to be an effective and safe therapy in patients with RA. Infliximab, in combination with oral or subcutaneous methotrexate, is administered intravenously, most commonly in an office-based setting. As with any intravenously administered protein, infusion-related adverse events have been reported with infliximab; however, such events are infrequent, and slowing the rate of the infusion may reduce their likelihood of occurring. These adverse events can generally be managed easily. Nurses who administer infliximab should have a thorough understanding of the product to prevent or manage adverse events. In this way, they can help ensure the safe delivery of the agent and optimize patient outcomes. | |
12771830 | Effect of femoral component design on unresurfaced patellas in knee arthroplasty. | 2003 May | Three total knee designs were evaluated to test the hypothesis that femoral component design affects the clinical and mechanical functions of the unresurfaced patella after total knee arthroplasty. Patients with the Ortholoc II, Advantim, and Profix femoral components were followed up for as many as 14 years and revision rate, anterior knee pain, and generalized knee pain were compared. A laboratory protocol was devised to evaluate pressure in the patellofemoral joint of knees from cadavers with a pressure-sensitive transducer using the same three designs at various degrees of knee flexion. Thirty Ortholoc II knee components were followed up for 14 years. Nineteen patients (63%) had severe anterior knee pain and 15 patients (50%) had reoperation to resurface the patella within 2 years. Two hundred one patients (222 knees) with Advantim components were followed up for 10 years and 305 patients (330 knees) with Profix components were followed up for 5 years. No patients with these two knee designs had severe anterior knee pain or reoperation for patellar resurfacing. A significantly higher rate of mild anterior knee pain was seen in the patients with Advantim components than in the patients with Profix components. No apparent relationship was seen between the severity of patellar wear found at the time of surgery and the incidence of anterior knee pain. Patients with rheumatoid arthritis receiving either the Advantim or Profix knee component performed as well as patients with osteoarthritis when the patella was not resurfaced. Pressure was significantly higher in the patellofemoral joints of the laboratory knee specimens with Ortholoc II components than in the specimens with either the Advantim or Profix components. The specimens with Advantim components had significantly higher pressure than did the specimens with normal knees, and the specimens with Profix components differed little from those with normal knees. | |
14989424 | Evidence for the biological modulation of IL-1 activity: the role of IL-1Ra. | 2002 Sep | Interleukin-1 (IL-1) and tumor necrosis factor (TNFalpha) are key mediators of inflammation and are produced by monocyte-macrophages (Mphi) following the activation of soluble factors and contact with stimulated Th1 lymphocytes. The contact between lymphocytes and Mphi is regulated by ligand and counterligands (i.e. beta2-integrins, CD40-CD40L, CD69) and plasma lipoproteins (i.e. HDL-associated Apo-AI). IL-1 and TNFalpha are potent inducers of matrix metalloproteinases (MMPs), eicosanoids, nitric oxide oxydase (iNOS), receptor activator of NF-kappaB ligand (RANKL), products involved in the destruction of the extracellular matrix, the cartilage and in bone resorption. IL-1--particularly important at the local level--is more potent than TNF in stimulating MMPs and specifically in impeding cartilage repair. However, IL-1 and TNFalpha strongly synergize in multiple biological functions. Blockade of IL-1 by IL-1 receptor antagonist (IL-1Ra, sIL-1RII) in combination with the soluble IL-1 accessory protein (IL-1R AcP) result in a long-term beneficial effect in chronic inflammatory diseases. The association with anti-TNF therapy may also represent a logical approach, considering the number of patients that do not respond to either compound alone. An altogether new challenge would be to accomplish the blockade at a more proximal level (i.e. lymphocyte/Mphi interaction). | |
15053128 | Avoiding pitfalls of correlation coefficients in the assessment of measurement instruments | 2004 Mar | OBJECTIVE: To provide a practical guide on how to avoid the pitfalls of correlated correlation coefficients when comparing multiple instruments in rehabilitation research. DESIGN: An observational study comparing a number of instruments measuring quality of life (QoL) compared with an external criterion. SUBJECTS: Sixty-eight patients admitted to a rheumatology ward for intensive treatment of rheumatoid arthritis. METHODS: Patients completed three new (QoL) instruments and an established instrument before and after intensive treatment for rheumatoid arthritis. MAIN OUTCOME MEASURES: Correlation coefficients together with their confidence intervals and a test for the difference between a set of correlated correlation coefficients for the change in the EuroQoL Quality of Life scale (EuroQoL), the World Health Organization Quality Of Life-Abbreviated version (WHOQoL-BREF) and the Quality of Life Profile (QLP) against the Stanford Health Assessment Questionnaire (HAQ). RESULTS: Although the range of correlation between the new instruments and the external criterion was between -0.37 and -0.59 and suggested that one new instrument was far more responsive than the others,; an omnibus test for an overall difference could find no difference in responsiveness. CONCLUSIONS: It is conceptually simple to use correlation coefficients to assess the properties of multiple instruments measured on the same subjects to find a 'best' instrument. However, proper interpretation of results when correlated correlation coefficients are calculated is complex. We recommend analysis includes: (a) that simple plots of the pairs of analysed variables are shown, (b) that simple linear model-fitting statistics, e.g., the R-squared statistic, accompany the plots, (c) that confidence intervals are presented for correlation coefficients, (d) that an omnibus statistical test for the difference between correlated correlation coefficients is presented, and (e) that normal model assumptions are tested. | |
14605648 | Postoperative therapy after metacarpophalangeal arthroplasty. | 2003 Oct | A literature review was conducted to determine the most effective postoperative therapy regimens for metacarpophalangeal (MCP) arthroplasty. The main difference between the regimens was the use of passive MCP extension over active extension and splinting in MCP flexion over splinting in extension. One study did not find continuous passive motion to be significantly beneficial for gaining hand strength or MCP motion. No study evaluated the efficacy or suitability of a particular regimen for specific implants or surgical procedures. | |
12709541 | Herbal medicines for the treatment of rheumatoid arthritis: a systematic review. | 2003 May | OBJECTIVE: With the growing interest in herbal therapies among persons with rheumatoid arthritis, there exists a need for investigation into their safety and efficacy. The purpose of this study was to conduct a systematic review to examine the evidence for the use of herbal medicines for RA based on randomized clinical trials (RCTs). METHODS: A computerized search of eight electronic databases and the bibliographies of identified articles resulted in 14 studies meeting the inclusion criteria. Two raters independently extracted data and rated the trials for quality. RESULTS: There is moderate support for gamma-linolenic acid (GLA), which is found in some herbal medicines, for reducing pain, tender joint count and stiffness. For other herbal medicines there was only a single RCT available, resulting in weak evidence. In general, herbal preparations were relatively safe to use. CONCLUSIONS: Given the number of herbal medicines promoted for RA, further research is needed to examine their efficacy, safety and potential drug interactions. | |
15549303 | Non-myeloablative stem cell transplantation for autoimmune diseases. | 2004 Nov | Treatment of life-threatening autoimmune diseases in animal models with induced or spontaneous autoimmune diseases can be accomplished by a 2-step procedure involving elimination of self-reactive lymphocytes with an immune ablative conditioning regimen followed by infusion of autologous or allogeneic stem cells, respectively. In animal models it was shown that using such a strategy, autoimmunity could be adequately controlled. It is speculated that de-novo development of the T and B cell repertoire from uncommitted progenitor cells in the presence of the autoantigens may be the best recipe for re-induction of self-tolerance, similarly to the normal ontogeny of the immune system during the induction of self tolerance in fetal stage. For both autologous and allogeneic hematopoietic stem cell transplantation, a non-myeloablative stem cell transplantation (NST) regimen may be used for safer lymphoablation rather than myeloablation. In addition, for allogeneic hematopoietic stem cell transplantation engraftment of disease resistant donor stem cells will alter the genetic predisposition towards autoimmune disease susceptibility. | |
12215863 | Weight bearing following intra-articular steroid injection of the knee: survey of current | 2002 Sep | INTRODUCTION: Intra-articular steroid therapy is one of the most common clinical procedures performed by rheumatologists. There is wide variation in the postoperative instructions given to patients following such injections. AIM: The aim of this study was to determine what advice is given with regards to non-weight-bearing following steroid injections of the knee by rheumatologists, orthopaedic surgeons, and general practitioners (GPs). METHOD: A questionnaire examining advice on non-weight-bearing following knee steroid injections was posted to 100 rheumatologists, 100 orthopaedic surgeons, and 50 GPs. RESULTS: A significant proportion of respondents advised patients to avoid weight bearing after injection (42.4%). Most of these advised patients to do so for one (16.3%) or two (25.1%) days. As compared to 57.1% of general practitioners and 2.8% of orthopaedic surgeons, 70.7% of rheumatologists advised patients to avoid weight bearing (P < 0.05). CONCLUSION: A significant proportion of rheumatologists and general practitioners performing steroid injections of the knee advise patients not to weight-bear postinjection. Examination of the available literature fails to reveal strong evidence to support such a practice, which has potentially significant implications with regards to loss of working days, costs of mobility aids, and patient inconvenience. |